Hayat Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Volume 5 - Role in Human Diseases
1. Auflage 2014
ISBN: 978-0-12-801054-9
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 338 Seiten

Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and up-to-date, this book offers a valuable guide to these cellular processes whilst inciting researchers to explore their potentially important connections. Volume 5 comprehensively describes the role of autophagy in human diseases, delivering coverage of the antitumor and protumor roles of autophagy; the therapeutic inhibition of autophagy in cancer; and the duality of autophagy's effects in various cardiovascular, metabolic, and neurodegenerative disorders. In spite of the increasing importance of autophagy in the various pathophysiological conditions mentioned above, this process remains underestimated and overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these and other diseases remains poorly understood. This book is an asset to newcomers as a concise overview of the diverse disease implications of autophagy, while serving as an excellent reference for more experienced scientists and clinicians looking to update their knowledge.ÿ Volumes in the Series

Autoren/Hrsg.

Hayat, M. A.

Inhaltsverzeichnis

1;Front Cover;1
2;Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging;4
3;Copyright Page;5
4;Dedication;6
5;Mitophagy and Biogenesis;8
6;Autophagy and Cancer;12
7;Contents;14
8;Foreword by Roberta A. Gottlieb;18
9;Foreword by Eeva-Liisa Eskelinen;20
10;Preface;22
11;Contributors;26
12;Abbreviations and Glossary;30
13;Autophagy: Volume 1 – Contributions;40
14;Autophagy: Volume 2 – Contributions;42
15;Autophagy: Volume 3 – Contributions;44
16;Autophagy: Volume 4 – Contributions;46
17;1 Introduction to Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Volume 5;48
17.1;Introduction;49
17.2;Specific Functions of Autophagy (A Summary);51
17.3;Autophagy in Normal Mammalian Cells;51
17.4;Endoplasmic Reticulum Stress and Autophagy;52
17.5;Major Types of Autophagies;53
17.5.1;Macroautophagy (Autophagy);54
17.5.2;Microautophagy;54
17.5.3;Chaperone-Mediated Autophagy;54
17.6;Autophagosome Formation;55
17.7;Autophagic Lysosome Reformation;56
17.8;Autophagic Proteins;57
17.8.1;Protein Degradation Systems;58
17.8.2;Beclin 1;58
17.8.3;Non-Autophagic Functions of Autophagy-Related Proteins;59
17.8.4;Microtubule-Associated Protein Light Chain 3;60
17.9;Monitoring Autophagy;60
17.10;Reactive Oxygen Species (ROS);61
17.11;Mammalian Target of Rapamycin (mTOR);61
17.12;Role of Autophagy in Tumorigenesis and Cancer;62
17.13;Role of Autophagy in Immunity;64
17.14;Autophagy and Senescence;66
17.15;Role of Autophagy in Viral Defense and Replication;66
17.16;Role of Autophagy in Intracellular Bacterial Infection;67
17.17;Role of Autophagy in Heart Disease;68
17.18;Role of Autophagy in Neurodegenerative Diseases;69
17.19;Cross-Talk between Autophagy and Apoptosis;71
17.20;Autophagy and Ubiquitination;75
17.21;Aggresome: Ubiquitin Proteasome and Autophagy Systems;76
17.22;Autophagy and Necroptosis;76
17.23;Mitochondrial Fusion and Fission;77
17.24;Selective Autophagies;78
17.24.1;Allophagy;78
17.24.2;Glycophagy;79
17.24.3;Pexophagy;84
17.25;References;88
18;I. Role of Autophagy in Cancer;96
18.1;2 Molecular Cross-Talk between the Autophagy and Apoptotic Networks in Cancer;98
18.1.1;Introduction;99
18.1.2;Dual Effector Molecules of Autophagy and Apoptosis;100
18.1.2.1;Bcl-2;100
18.1.2.2;Beclin;101
18.1.2.3;Atg5;102
18.1.2.4;Atg12;102
18.1.2.5;UVRAG;103
18.1.3;Molecular Cross-Talk between Autophagy and the UbiqUitin + Proteasome System;103
18.1.4;Molecular Linkage of the Ups with Aggresomes and Selective Autophagy;107
18.1.5;Conclusion;108
18.1.6;References;109
18.2;3 Inhibition of ErbB Receptors and Autophagy in Cancer Therapy;112
18.2.1;Introduction;113
18.2.2;Autophagy;113
18.2.3;ErbB Family of Receptor Tyrosine Kinases;114
18.2.4;EGFR (ErbB1) and Autophagy;116
18.2.5;ErbB2 (HER2/NEU) and Autophagy;121
18.2.6;ErbB3 and ErbB4 and Autophagy;123
18.2.7;Discussion;123
18.2.8;Acknowledgments;125
18.2.9;References;125
18.3;4 Ginsenoside F2 Initiates an Autophagic Progression in Breast Cancer Stem Cells;128
18.3.1;Introduction;129
18.3.2;Autophagy;129
18.3.2.1;Major Molecular Components in Autophagy;129
18.3.2.2;Cross-Talk between Apoptosis and Autophagy;130
18.3.3;Autophagy Induced by Ginsenoside F2 in Breast Cancer Stem Cells;130
18.3.3.1;Ginsenoside F2 Induces Autophagy in Breast CSCs;130
18.3.3.2;F2 Induces Autophagy through the Modulation of p53;131
18.3.3.3;Mechanism for the Effects of F2 on Breast CSCs;131
18.3.4;Discussion;134
18.3.5;Acknowledgments;136
18.3.6;References;136
18.4;5 Role of Autophagy in Cancer Therapy;138
18.4.1;Introduction;139
18.4.2;Autophagy and Cell Signaling;140
18.4.3;Autophagy and Cell Death: Implication in Cancer;142
18.4.4;The Role of Autophagy in Cancer is Context Dependent: Oncogene Transformation Versus Established Tumors;144
18.4.5;Mitophagy, ROS, and Cancer;145
18.4.6;Cancer Stem Cells and Autophagy;146
18.4.7;Cancer Therapy by Modulating Autophagy;147
18.4.8;Discussion;147
18.4.9;References;149
18.5;6 Autophagy in Human Brain Cancer: Therapeutic Implications;152
18.5.1;Introduction;153
18.5.2;Background on Autophagy;154
18.5.3;Autophagy and its Flux;155
18.5.3.1;Autophagy-Dependent Control of Cell Survival and Cell Death;156
18.5.4;Expression of Autophagy Regulators and Associated Factors in Human Glioblastoma Tissue;157
18.5.5;Signaling Pathways, miRNA Regulating Autophagy, and Glioblastoma;159
18.5.6;Therapeutic Perspectives Related to Autophagy in Glioblastoma;161
18.5.6.1;Should We Switch Autophagy On or Off in Order to Combat Glioblastoma?;161
18.5.6.2;Autophagy Inhibitors in Cancer Treatment;161
18.5.6.3;Autophagy Inducers in Cancer Treatment;163
18.5.7;Switch between Apoptosis and Autophagy;165
18.5.8;Conclusion;166
18.5.9;References;166
18.6;7 Blockage of Lysosomal Degradation Is Detrimental to Cancer Cell Survival: Role of Autophagy Activation;168
18.6.1;Introduction;169
18.6.2;Lysosomes;170
18.6.2.1;Normal Function of Lysosomes;170
18.6.2.2;Lysosomal Hydrolases;170
18.6.2.3;Cathepsin D;171
18.6.2.4;Cathepsins B and L;171
18.6.2.5;Pathways Converging in Lysosomes;172
18.6.2.6;Lysosomal Regulation of Autophagy;172
18.6.2.7;Lysosomal Membrane Permeability (LMP);173
18.6.3;Blockage of Lysosomal Degradation in Cancer;173
18.6.3.1;Insufficient Lysosomal Function Impairs Autophagy;174
18.6.3.2;Targeting Cathepsins in the Treatment of Cancer;174
18.6.3.3;Targeting Lysosomes in Cancer Therapy;176
18.6.4;Discussion;177
18.6.5;Acknowledgments;179
18.6.6;References;179
18.7;8 Induction of Protective Autophagy in Cancer Cells by NAE Inhibitor MLN4924;182
18.7.1;Introduction;183
18.7.2;Autophagy;183
18.7.2.1;Characteristics of Autophagy;183
18.7.2.2;Autophagy in Tumorigenesis and Anticancer Therapy;184
18.7.3;Neddylation;185
18.7.3.1;Post-translational Modification via Neddylation;185
18.7.3.2;Neddylation Substrate cullin-RING E3 Ligase (CRL) as an Anticancer Target;185
18.7.4;MLN4924, a Small Molecule Inhibitor of NAE;186
18.7.4.1;NAE Enzyme Inhibitor MLN4924 as a First-In-Class Anticancer Agent;186
18.7.4.2;MLN4924 Triggers Autophagic Responses in Cancer Cells;186
18.7.4.3;MLN4924-Induced Autophagy is Protective and Serves as a Survival Signal;186
18.7.4.4;Critical Role of the mTOR–DEPTOR Axis in MLN4924-Induced Autophagy;187
18.7.5;Discussion;187
18.7.6;References;189
18.8;9 Effect of Autophagy on Chemotherapy-Induced Apoptosis and Growth Inhibition;192
18.8.1;Introduction;193
18.8.2;Autophagy and Chemotherapy-Induced Apoptosis and Growth Inhibition;194
18.8.2.1;Autophagy Restrains Chemotherapy-Induced Apoptosis;194
18.8.2.2;Autophagy Promotes Chemotherapy-Induced Apoptosis;195
18.8.2.3;Autophagy Aggravates Chemotherapy-Induced Growth Inhibition;196
18.8.3;Autophagy, Tumor Microenvironment, and Chemoresistance;196
18.8.3.1;Hypoxia-Induced Autophagy Contributes to Chemoresistance of Tumor Cells;196
18.8.3.2;Hypoxia-Induced Autophagy Contributes to Tolerance of Tumor Cells to Nutrient Deprivation in Tumor Microenvironment;197
18.8.4;Autophagy and DNA Damage-Inducing Chemotherapy;198
18.8.4.1;Autophagy Can Be Induced by DDRs in DNA Damaged Cells;198
18.8.4.2;Autophagy Regulates DDRs by Indirect and Direct Approaches;199
18.8.4.3;Autophagy Essential Proteins Regulate DDR by Autophagy-Independent Means;199
18.8.5;Autophagy and Cancer Stem Cells in Chemoresistance;199
18.8.5.1;Autophagy Is Essential for Maintenance of the Tumorigenicity of CSCs;199
18.8.5.2;Autophagy Contributes to Survival of CSCs in Oxygen and/or Nutrient-Deprived Tumor Microenvironment;200
18.8.5.3;Autophagy Involved in CSC Chemoresistance;200
18.8.6;Conclusion;201
18.8.7;References;201
18.9;10 Autophagy Upregulation Reduces Doxorubicin-Induced Cardiotoxicity;204
18.9.1;Introduction;205
18.9.2;Anthracycline-Induced Cardiotoxicity;206
18.9.2.1;What Is Cardiotoxicity?;206
18.9.2.2;Classification of Anthracycline-Induced Cardiotoxicity;206
18.9.2.3;Mechanisms of Cardiotoxicity;207
18.9.3;The Oxidative Stress Hypothesis;209
18.9.4;Autophagy;211
18.9.4.1;Signaling Pathways Regulating Autophagy;212
18.9.4.2;Oxidative Stress and Autophagy;213
18.9.4.3;The Role of Autophagy in Heart Disease and Cancer;214
18.9.5;Autophagy Induction as a Mechanism to Reduce Doxorubicin-Induced Cardiotoxicity;215
18.9.6;Summary;217
18.9.7;Acknowledgments;218
18.9.8;References;218
19;II. Role of Autophagy in Cardiovascular, Metabolic, and Neurodegenerative Diseases;222
19.1;11 Autophagy in Critical Illness;224
19.1.1;Introduction;224
19.1.1.1;The Formation and Regulation of Autophagy;225
19.1.2;Autophagy in Critical Illness – the Role of Nutrient Restriction, Deprivation, and/or Starvation;227
19.1.3;Autophagy in Brain Injury;228
19.1.3.1;Basal Neuronal Autophagy;228
19.1.3.2;Traumatic Brain Injury;228
19.1.3.3;Intracerebral and Subarachnoid Hemorrhage;229
19.1.4;Autophagy in Infection and Inflammation;230
19.1.5;Therapeutic Target;234
19.1.6;References;235
19.2;12 Autophagy in the Onset of Atrial Fibrillation;240
19.2.1;Introduction;241
19.2.2;Mechanisms of Atrial Fibrillation;241
19.2.3;Drugs used for Treating Atrial Fibrillation;242
19.2.4;Autophagy in Atrial Fibrillation;243
19.2.5;Potential Role of Modulators of Autophagy in the Treatment of Atrial Fibrillation;245
19.2.6;Conclusion;246
19.2.7;Acknowledgments;246
19.2.8;References;246
19.3;13 Role of Autophagy in Atherogenesis;250
19.3.1;Introduction;251
19.3.2;Autophagy in the Major Cell Types Involved in Atherosclerosis;251
19.3.2.1;Endothelial Cells;251
19.3.2.2;Vascular Smooth Muscle Cells (VSMCs);252
19.3.2.3;Macrophages;253
19.3.3;Role of Autophagy in Lipid Metabolism;253
19.3.3.1;Autophagy and ApoB-containing Lipoproteins;253
19.3.3.2;Autophagy and Sterol Regulatory Element Binding Proteins (SREBPs): A Two-Way Regulatory Pathway;254
19.3.3.3;Autophagy, Cholesterol Efflux, and Reverse Cholesterol Transport;254
19.3.4;Recent Discoveries About Autophagy and Atherosclerosis in Animal Models;255
19.3.5;Autophagy: A Target for Atherosclerosis Treatment;256
19.3.6;Conclusion;256
19.3.7;Acknowledgments;256
19.3.8;References;256
19.4;14 Regulation of Autophagy in Insulin Resistance and Type 2 Diabetes;260
19.4.1;Introduction;261
19.4.2;Main Regulatory Mechanisms;262
19.4.2.1;Nutrients and Growth Factors;262
19.4.2.2;Energy Status;262
19.4.2.3;Endoplasmic Reticulum Stress;262
19.4.2.4;Forkhead Box O (FoxO) Transcription Factors;264
19.4.3;Regulation of Autophagy in Insulin Resistance or T2DM in Different Organs;264
19.4.3.1;Liver;264
19.4.3.2;White Adipose Tissue;267
19.4.3.3;Pancreatic Beta Cells;270
19.4.3.4;Hypothalamus;272
19.4.3.5;Myocardium;274
19.4.3.6;Skeletal Muscle;277
19.4.4;Conclusion;280
19.4.5;Acknowledgments;280
19.4.6;References;281
19.5;15 Pancreatic Beta Cell Autophagy and Islet Transplantation;284
19.5.1;Introduction;285
19.5.1.1;Crinophagy in Beta Cells;285
19.5.1.2;Autophagy and Beta Cell Function;285
19.5.2;Induction of Autophagy in MIN6 Cells and in Human Islets;286
19.5.3;Fatty Acids, Beta Cell Autophagy, and Lipotoxicity;287
19.5.4;Beta Cell Autophagy in Diabetes;288
19.5.5;CrossTalk between Autophagy and Apoptosis;288
19.5.6;Autophagy in the Islet Transplantation Setting;289
19.5.7;Hypoxia and Autophagy;290
19.5.8;Targeting Autophagy to Improve the Survival of Transplanted Islets;292
19.5.9;References;293
19.6;16 Autophagy Guards Against Immunosuppression and Renal Ischemia-Reperfusion Injury in Renal Transplantation;296
19.6.1;Introduction;297
19.6.2;Basal Autophagic Activity;297
19.6.3;Autophagy and I/R Injury;299
19.6.4;Protective Mechanisms;300
19.6.5;Autophagy and ImmunosuppresSants;301
19.6.6;Autophagy and Metabolic Stress;302
19.6.7;Discussion;303
19.6.8;References;304
19.7;17 When the Good Turns Bad: Challenges in the Targeting of Autophagy in Neurodegenerative Diseases;306
19.7.1;Introduction;307
19.7.2;Briefly: The Highly Regulated Autophagy Pathway;307
19.7.3;Autophagy Modulation in Neurodegenerative Diseases;309
19.7.4;Autophagy Impairment and Neurodegeneration: When the Good Becomes Bad;311
19.7.4.1;Defects of Autophagy Induction;311
19.7.4.2;Alterations in Nucleation/Autophagosome Formation;314
19.7.4.3;Vesicle Expansion Perturbations;314
19.7.4.4;Abnormal Cargo Recognition;315
19.7.4.5;Crossroads of Autophagy and Endocytosis;316
19.7.4.6;Autophagosome Clearance Alterations;317
19.7.5;Conclusions and Perspectives;317
19.7.6;Acknowledgments;318
19.7.7;References;318
19.8;18 The a-Tubulin Deacetylase HDAC6 in Aggresome Formation and Autophagy: Implications for Neurodegeneration;320
19.8.1;Introduction;321
19.8.2;Cytoskeletal Proteins as Targets for the Deacetylase Functions of HDAC6;322
19.8.3;The Role of HDAC6 in Aggresome Formation and Autophagy;323
19.8.3.1;Aggresome Formation and HDAC6;323
19.8.3.2;HDAC6 and Autophagy;325
19.8.3.3;HDAC6 and Heat Shock Responses;325
19.8.4;HDAC6 and Neurodegeneration;326
19.8.5;Acknowledgments;327
19.8.6;References;327
20;Index;330

Leseproben

Chapter 1 Introduction to Autophagy
Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Volume 5
M.A. Hayat Autophagy plays a direct or indirect role in health and disease. A simplified definition of autophagy is that it is an exceedingly complex process which degrades modified, superfluous (surplus) or damaged cellular macromolecules and whole organelles using hydrolytic enzymes in the lysosomes. It consists of sequential steps of induction of autophagy, formation of autophagosome precursor, formation of autophagosomes, fusion between autophagosome and lysosome, degradation of cargo contents, efflux transportation of degraded products to the cytoplasm, and lysosome reformation. This chapter discusses specific functions of autophagy, the process of autophagy, major types of autophagy, influences on autophagy, and the role of autophagy in disease, immunity, and defense. Keywords
Autophagy; aging; disease; apoptosis; lysosomes Outline Introduction 2 Specific Functions of Autophagy (A Summary) 4 Autophagy in Normal Mammalian Cells 4 Endoplasmic Reticulum Stress and Autophagy 5 Major Types of Autophagies 6 Macroautophagy (Autophagy) 7 Microautophagy 7 Chaperone-Mediated Autophagy 7 Autophagosome Formation 8 Autophagic Lysosome Reformation 9 Autophagic Proteins 10 Protein Degradation Systems 11 Beclin 1 11 Non-Autophagic Functions of Autophagy-Related Proteins 12 Microtubule-Associated Protein Light Chain 3 13 Monitoring Autophagy 13 Reactive Oxygen Species (ROS) 14 Mammalian Target of Rapamycin (mTOR) 14 Role of Autophagy in Tumorigenesis and Cancer 15 Role of Autophagy in Immunity 17 Autophagy and Senescence 19 Role of Autophagy in Viral Defense and Replication 19 Role of Autophagy in Intracellular Bacterial Infection 20 Role of Autophagy in Heart Disease 21 Role of Autophagy in Neurodegenerative Diseases 22 Cross-Talk Between Autophagy and Apoptosis 24 Autophagy and Ubiquitination 28 Aggresome: Ubiquitin Proteasome and Autophagy Systems 29 Autophagy and Necroptosis 29 Mitochondrial Fusion and Fission 30 Selective Autophagies 31 Allophagy 31 Glycophagy 32 Lipophagy 33 Mitophagy 35 Nucleophagy 36 Pexophagy 37 Reticulophagy 38 Ribophagy 39 Xenophagy 40 Zymophagy 40 References 41 Introduction
Aging has so permeated our lives that it cannot be stopped, but it can be delayed. Under the circumstances, time is our only friend. Because the aging process is accompanied by disability and disease (for example, Alzheimer’s and Parkinson’s conditions) and cannot be prevented, it seems that slow aging is the only way to have a healthy longer life. In general, aging can be slowed down by not smoking or chewing tobacco, by preventing or minimizing perpetual stress (anger, competition), by abstinence from alcoholic beverages, by regular exercise, and by having a healthy diet. There is no doubt that regular physical activity is associated with a reduced risk of mortality and contributes to the primary and secondary prevention of many types of diseases. Discipline is required to attain this goal. Regarding the role of a healthy diet, a caloric restriction induces autophagy that counteracts the development of age-related diseases and aging itself. On the other hand, autophagy is inhibited by high glucose and insulin-induced P13K signaling via Akt and mTOR. Based on its fundamental roles in these and other disease processes’ prevention and therapy, autophagy has emerged as a potential target for disease. Unfortunately, inevitable death rules our lives, and a group of abnormal cells plays a part in it. Safe disposal of cellular debris is crucial to keep us alive and healthy. Our body uses autophagy and apoptosis as clearing mechanisms to eliminate malfunctioning, aged, damaged, excessive, and/or pathogen-infected cell debris that might otherwise be harmful/autoimmunogenic. However, if such a clearing process becomes uncontrollable, it can instead be deleterious. For example, deficits in protein clearance in brain cells because of dysfunctional autophagy may lead to dementia. Autophagy can also promote cell death through excessive self-digestion and degradation of essential cellular constituents. Humans and other mammals with long lifespans unfortunately have to face the problem of the accumulation of somatic mutations over time. Although most of the mutations are benign and only some lead to disease, there are too many of them. Cancer is one of these major diseases, and is caused by a combination of somatic genetic alterations in a single cell, followed by uncontrolled cell growth and proliferation. Even a single germline deletion of or mutation in a tumor suppressor gene (e.g., p53) predisposes an individual to cancer. It is apparent that nature tries to ensure the longevity of the individual by providing tumor suppressor genes and other protective mechanisms. Autophagy (Beclin 1 gene) is one of these mechanisms that plays an important role in influencing the aging process. Autophagy research is in an explosive phase, driven by a relatively new awareness of the enormously significant role it plays in health and disease, including cancer, other pathologies, inflammation, immunity, infection, and aging. The term autophagy (auto phagin, from the Greek meaning self-eating) refers to a phenomenon in which cytoplasmic components are delivered to the lysosomes for bulk or selective degradation under the lysosomes’ distinct intracellular and extracellular milieu. This term was first coined by de Duve over 46 years ago (Deter and de Duve, 1967), based on the observed degradation of mitochondria and other intracellular structures within lysosomes of rat liver perfused with the pancreatic hormone glucagon. Over the past two decades an astonishing advance has been made in the understanding of the molecular mechanisms involved in the degradation of intracellular proteins in yeast vacuoles and the lysosomal compartment in mammalian cells. Advances in genome-scale approaches and computational tools have presented opportunities to explore the broader context in which autophagy is regulated at the systems level. A simplified definition of autophagy is that it is an exceedingly complex process which degrades modified, superfluous (surplus), or damaged cellular macromolecules and whole organelles using hydrolytic enzymes in the lysosomes. Autophagy can be defined in more detail as a regulated process of degradation and recycling of cellular constituents participating in organelle turnover, resulting in the bioenergetic management of starvation. This definition, however, still represents only some of the numerous roles played by the autophagic machinery in mammals; most of the autophagic functions are listed later in this chapter. Autophagy plays a constitutive and basally active role in the quality control of proteins and organelles, and is associated with either cell survival or cell death. Stress-responsive autophagy can enable adaptation and promote cell survival, whereas in certain models, autophagy has also been associated with cell death, representing either a failed attempt at survival or a mechanism that supports cell and tissue degradation. Autophagy prevents the accumulation of random molecular damage in long-lived structures, particularly mitochondria, and more generally provides a means to reallocate cellular resources from one biochemical pathway to another. Consequently, it is upregulated in conditions where a cell is responding to stress signals, such as starvation, oxidative stress, and exercise-induced adaptation. The balance between protein and lipid biosynthesis, and their eventual degradation and resynthesis, is one critical component of cellular health. Degradation and recycling of macromolecules via autophagy provides a source of building blocks (amino acids, fatty acids, sugars) that allow temporal adaptation of cells to adverse conditions. In addition to recycling, autophagy is required for the degradation of damaged or toxic material that can be generated as a result of ROS accumulation during oxidative stress. The mitochondrial electron transport chain and the peroxisomes are primary sources of ROS production in most eukaryotes. Specific Functions of Autophagy (A Summary)
Autophagy plays a direct or indirect role in health and disease, including, among others, control of embryonic and early postnatal development; tissue homeostasis (protein and cell organelle turnover); mitochondrial quality control; protection of cells from stresses; survival response to nutrient deprivation; cellular survival or physiological cell death...